The use and effectiveness of many therapeutic agents is limited by the solubility of the agents. Taxanes like paclitaxel and docetaxel are chemotherapy agents that are commonly used in the treatment of breast, lung, prostate and other cancers. Taxanes interfere with the microtubules in the cancer cell, stopping the cell from dividing and causing its death. Unfortunately, the use and effectiveness of taxanes is limited by the solubility of the agents.
Taxol® and Taxotere®, two leading cancer therapeutics, are formulations of the minimally water-soluble antitumor agents paclitaxel (PTX) and docetaxel (DTX), respectively, solubilized in the adjuvants Cremophor EL® and polysorbate 80 (Tween 80®), respectively. However, Taxol® and Taxotere® contain only about 1 and 4 wt %, respectively, of the actives. The large amount of the surfactant/excipient/carrier that accompanies drug dosage leads to a range of undesirable side effects. For example, many patients show acute hypersensitivity response to Cremophor EL® present in Taxol®; 1.5-3% suffer major, potentially life-threatening reactions. Abraxane® is an alternative formulation of PTX in which a “human albumin-stabilized, lyophilized NP formulation” is used instead of Cremophor EL®. Abraxane® contains ca. 10 wt % PTX, and is approved only for second-line metastatic breast cancer patients. Clearly there is a need for developing improved formulations for taxane (and other similarly hydrophobic) antitumor agents.
There is currently a need for methods to modify the solubility of certain therapeutic agents to improve their ability to be administered as therapeutics. There is also a need for new formulations and for formulating methods that can be used to deliver therapeutic agents to patients. In particular, there is a need for formulations that have higher drug loading (i.e., less excipient), that can be localized preferentially at a tumor site, or that selectively release their drug payload in the environment (e.g. more acidic) of the tumor.